A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy

NCT04666740 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-481
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 7

Brief Summary

The study researchers think that combining the drugs pembrolizumab and olaparib (POLAR) may help people with this disease because pembrolizumab activates the immune system to fight cancer, and olaparib destroys cancer cells by preventing them from repairing damage to the genetic information that helps them survive and grow. The study researchers are doing this study to find out whether combining these drugs may be a more effective treatment for this cancer than taking olaparib alone.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma; Homologous Recombination Deficiency (HRD)

Keywords

Pembrolizumab; OLApaRib (POLAR); 20-481

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS is defined as the time from the initiation of study treatment to radiographic progression or death.

  6 months

Secondary Outcomes (1)

• Overall survival (OS)

  6 months

Study Arms (3)

Cohort A: Core HRD

EXPERIMENTAL

Patients with either pathogenic germline or somatic alterations of 3 core homologous recombination-genes (HR-genes) - (BRCA1/2, or PALB2) who have stable or responding disease on first-line or second-line platinum therapy in two consecutive imaging assessments over at least 4 months are eligible for inclusion in Cohort A.

Drug: Pembrolizumab; Drug: Olaparib

Cohort B: Non core HRD

EXPERIMENTAL

Patients with either pathogenic somatic or germline non-core 14 HR-gene alterations (ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, RTEL1) who have stable or responding disease on first-line or second-line platinum therapy in two consecutive imaging assessments over at least 4 months are eligible for inclusion in Cohort B.

Drug: Pembrolizumab; Drug: Olaparib

Cohort C: Platinum sensitive

EXPERIMENTAL

Patients without any of the above HR-gene alterations included in Cohort A and B who have platinum-sensitivity, which is defined as a partial response (PR) or complete response (CR) for the best overall response (BOR) during at least 4 months on platinumbased therapy. Variants of unknown significance of candidate HR-genes from Cohort A or B will be eligible for Cohort C if they meet the partial response to platinum criterion.

Drug: Pembrolizumab; Drug: Olaparib

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV every 3 week. After the first 6 months (8 cycles), on C9D1 Pembrolizumab 400 mg IV every 6 week.

Cohort A: Core HRD; Cohort B: Non core HRD; Cohort C: Platinum sensitive

Olaparib DRUG

Olaparib 300 mg twice day orally daily continuously (POLAR) as a maintenance therapy. After the first 6 months (8 cycles), on C9D1 olaparib 300 mg twice a day orally will be continued.

Cohort A: Core HRD; Cohort B: Non core HRD; Cohort C: Platinum sensitive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• This is an on-platinum maintenance trial either in a first-line or second-line setting.
• Participants must have either stable disease or responding disease on current first-line or second-line platinum treatment for metastatic disease.
• Male or female patients with cytologically or histologically confirmed metastatic pancreas adenocarcinoma or acinar cell carcinoma with homologous recombination gene alterations or platinum sensitivity.
• Patients will be assigned to cohorts based on their genetic alterations and clinical response.
• Patient stratification to different Cohorts will be in the order of more canonical homologous recombination-gene (HR-gene) order. For example, patients who meet criteria for both A and B Cohorts, they will be assigned to Cohort A, not B. Cohorts will be defined as following by CLIA-approved NGS or MSK-IMPACT Part A or C:
• Cohort C: Patients without any of the above HR-gene alterations included in Cohort A and B who have platinum-sensitivity, which is defined as a partial response (PR) or complete response (CR) for the best overall response (BOR) during at least 4 months on platinum-based therapy. Variants of unknown significance of candidate HR-genes from Cohort A or B will be eligible for Cohort C if they meet the partial response to platinum criterion.
• Variants of unknown significance (VUS) or benign polymorphisms of above 17 HR-genes from Cohort A and B are considered non-pathogenic and will be excluded from cohort A or B. However, if the participant demonstrates platinum sensitivity, patient can be considered eligible for Cohort C.
• A recurrence after curative surgery is eligible if the recurrence is \> 6 months after the last date of adjuvant therapy and the participant has at least stable or responding disease on platinum therapy and meet the above genomic or platinum sensitivity criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 .
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined as below:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Platelets ≥100 000/μL
• Total bilirubin ≤ 2 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for if liver metastases)

You may not qualify if:

• Disease progression on either a first-line or the second-line platinum for metastatic PDAC or acinar cell carcinoma.
• Patients with a second (or more) primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 cancers or low grade lymphomas curatively treated, without evidence of disease, and not requiring any active treatment prior to study entry are eligible
• Resting EKG with QTC ≥ 450 msec detected on 2 or more time points within a 24-hour period or family history of long QT syndrome. If EKG demonstrates QTC ≥ 450 msec, patient will only be eligible if repeat EKG demonstrates QTC ≤ 450 msec.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Previous allogeneic bone marrow transplant.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required for eligibility. The patient can receive a stable dose of corticosteroids before and during the study as long as the steroids were started at least 4 weeks prior to treatment and the steroid dose is \< 10 mg/day. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Patients with known active hepatitis (i.e. Hepatitis B or C).
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Has a known history of active TB (Bacillus tuberculosis).
• Any prior treatment with any PARP inhibitor, including olaparib.
• Any previous treatment with any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Monmouth (All protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All protocol activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (All protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Basking Ridge (All protocol activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, 11553, United States

Location

Related Publications (2)

• Park W, O'Connor CA, Chou JF, Hilmi M, Tarcan Z, Schwartz C, Larsen M, Homsi R, Sivaprakasam K, Umeda S, Perry MA, Varghese AM, Yu KH, Balogun F, Zervoudakis A, Katz SS, Kim TH, Zhao K, Richards AL, Lecomte N, Martin Muldoon D, Karnoub E, Chatila W, Yang J, El-Dika I, Rao D, Joshi S, Foote MB, Sugarman R, Harding JJ, Epstein AS, Kelsen D, Chalassani S, Keane F, Schoenfeld JD, Singhal A, Diguglielmo E, Bandlamudi C, Song J, Ozkan HS, Hong J, Zhang H, Cardenas AI, Lao M, Melchor J, Shah R, Kang W, Mazzoni F, Soares K, Donoghue MT, Santos E, Rolston V, Reyngold M, Wei AC, Tipping M, Basturk O, Berger M, Kihn Do R, Schattner M, Jarnagin WR, Riaz N, Balachandran V, Pe'er D, Capanu M, Iacobuzio-Donahue C, O'Reilly EM. Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial. Nat Med. 2026 Mar 25. doi: 10.1038/s41591-026-04299-5. Online ahead of print.

  PMID: 41882405 DERIVED

• Park W, O'Connor C, Chou J, Hilmi M, Tarcan Z, Schwartz C, Larsen M, Chatila W, Sivaprakasam K, Umeda S, Perry M, Varghese A, Yu K, Balogun F, Zervoudakis A, Katz S, Kim TH, Zhao K, Richards A, Lecomte N, Muldoon D, Karnoub E, Yang J, El-Dika I, Rao D, Smita J, Foote M, Sugarman R, Harding J, Epstein A, Kelsen D, Chalasani S, Keane F, Schoenfeld J, Singhal A, Diguglielmo E, Bandlamudi C, Song J, Ozkan HS, Hong J, Zhang H, Cardenas A, Lao M, Melchor J, Shah R, Kang W, Mazzoni F, Soares K, Donoghue M, Balachandran V, Schattner M, Santos E, Rolston V, Reyngold M, Wei A, Homsi R, Tipping M, Basturk O, Berger M, Do R, Jarnagin W, Riaz N, Pe'er D, Capanu M, Iacobuzio-Donahue C, O'Reilly E. Pembrolizumab and Olaparib (POLAR) Maintenance Therapy in Metastatic Pancreatic Cancer With or Without Homologous Repair Deficiency: A Biomarker Selected Phase II Trial. Res Sq [Preprint]. 2025 Sep 1:rs.3.rs-7334701. doi: 10.21203/rs.3.rs-7334701/v1.

  PMID: 40951294 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

pembrolizumab; olaparib

Study Officials

• Wungki Park, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 2, open-label, non-randomized study.

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 14, 2020
• Study Start: December 18, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)